Sickle Cell Disease - Stroke Prevention in Nigeria Trial (SPIN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Vanderbilt University
Sponsor:
Collaborators:
Aminu Kano Teaching Hospital
Information provided by (Responsible Party):
Michael DeBaun, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01801423
First received: February 26, 2013
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

Given large absolute numbers of individuals with sickle cell disease in Nigeria, hydroxyurea therapy for all individuals with sickle cell disease may not be initially feasible; however, a targeted strategy of hydroxyurea use for primary prevention of strokes is an alternative to the standard therapy (observation) for high-risk individuals. The investigators propose a feasibility study, Sickle Cell Disease - Stroke Prevention in Nigeria (SPIN) Trial, to determine whether hydroxyurea can be used for primary prevention of strokes in Nigerian children with sickle cell anemia.


Condition Intervention Phase
Sickle Cell Anemia
Sickle Cell Disease
Stroke
Drug: Hydroxyurea
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sickle Cell Disease - Stroke Prevention in Nigeria Trial

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Hydroxyurea Therapy Acceptance and Adherence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The primary outcome measure will be adherence to daily administration of hydroxyurea. If adherence rate is less than 55%, alternative strategies must be considered for the definitive Phase III Trial.


Secondary Outcome Measures:
  • Hydroxyurea Safety protocol for Children with Sickle Cell Anemia [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    We will evaluate the use of a standard safety protocol, non-dose escalating, for hydroxyurea in children with sickle cell anemia using a protocol similar to the recently completed National Heart Lung and Blood Institute (NHLBI) Baby HUG study, published in Lancet.(1) We expect the proportion of serious adverse reactions, as well as hydroxyurea-related morbidity and mortality, to be very small compared to the benefits. We will compare the frequency of severe adverse events and hydroxyurea toxicity related events that are associated with hospitalization in those receiving hydroxyurea (n= 40) to those who had normal transcranial Doppler measurements (n= 210) over the course of one year.


Other Outcome Measures:
  • Feasibility of a Definitive Phase III Trial for Hydroxyurea Therapy to Prevent Strokes in Sickle Cell Disease [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    During the course of the current study, we will prepare a manual of operations and case report forms for the proposed trial. We will also solidify working relationships with our colleagues and collaborators at Aminu Kano Teaching Hospital in Kano, Nigeria; and develop and organize all committees, collaborators and study procedures necessary for initiation of a successful, definitive, Phase III Trial.


Estimated Enrollment: 40
Study Start Date: February 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydroxyurea
We propose to enroll 40 children with SCA and an elevated TCD measurement between 5 and 12 years of age in this one arm feasibility study of hydroxyurea therapy, with follow-up of at least 12 months per subject. The study intervention will include HU to begin at ~ 20 mg/kg/day(range 17.5 - 26 mg/kg/day). No dose escalation will occur. Given the success of the first year of enrollment and the favorable response of TCD measurement after 3 months on HU therapy, the study investigators have participants as an internal pilot. The definitive phase III trial will now compare low dose HU therapy to the result of no treatment arm from the STOP Trial.
Drug: Hydroxyurea
Hydroxyurea will be prescribed as an investigational therapy by the treating physician. Recommended guidelines for titration of hydroxyurea to maximal tolerated dose are below. The study intervention will include hydroxyurea to begin at ~20 mg/kg/day (range 17.5 - 26 mg/kg/day). No dose escalation will occur as this dose was shown to have some efficacy in infants with SCA and was associated with rare myelosuppression.(1)
Other Names:
  • Droxia
  • Hydrea
  • Mylocel

  Eligibility

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Screening:

  • Patients with hemoglobin SS or S beta zero thalassemia confirmed by hemoglobin electrophoresis;
  • Informed consent from a parent or legal guardian and assent of participant ages 5 through 12;
  • Successful completion of screening procedures: cerebral blood flow velocity ≥ 200 cm/sec in the terminal portion of internal carotid or middle cerebral artery;
  • Patient must be 5 through 12 years of age (i.e., must have attained their 5th but not their 13th birthday when the consent is signed).

Exclusion Criteria for Screening:

  • Prior overt stroke (a focal neurological deficit of acute onset) by history, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening (an established tool in resource poor countries).(2,3) A "positive" screening is defined as answering yes to any one of the 10 questions. The negative predictive value (child does not have moderate or several neurological impairment) of the "10 questions" is greater than 94% in children (2);
  • Other exclusions: significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless Hb is > 9 g/dl], renal insufficiency (creatinine > 0.8 mg/dl); other significant organ system dysfunction, or other contraindication to hydroxyurea therapy; and history of seizures or diagnosis of epilepsy;
  • Patients for whom hydroxyurea therapy is under consideration prior to study consent/education;
  • Patients who have previously been treated with hydroxyurea and are being considered to restart hydroxyurea therapy;
  • Other significant organ system dysfunction;
  • Any other condition or chronic illness, which in the opinion of the site's Principal Investigator (PI) makes participation ill-advised or unsafe.
  • Participants of child bearing age who are pregnant or may become pregnant should not take hydroxyurea. If a participant becomes pregnant during the study, their hydroxyurea treatment will be stopped immediately. The onsite will notify the clinical coordinating center and the principal investigators of the case. The site principal investigator and study principal investigators will determine what therapy the participant should receive during pregnancy that is of standard care.

Inclusion Criteria for Study Therapy:

  • Successful completion of screening procedures inclusive of cerebral blood flow velocity greater than or equal to 200 cm/sec measured twice or at least one measurement greater than or equal to 220 cm/sec in the terminal portion of internal carotid and middle cerebral artery;
  • Informed consent from a parent or legal guardian for study therapy and assent of the participant completed;
  • Participant is able to swallow a capsule as observed by study personnel;
  • Acceptance of hydroxyurea therapy for one year.

Exclusion Criteria for Treatment Group:

- Unable to commit to follow up visits for the course of the study.

Inclusion Criteria for participants that are not eligible to receive hydroxyurea therapy, but will be followed for one year (control group):

  • Successful completion of screening procedures inclusive of cerebral blood flow velocity less than or equal to 199 cm/sec in the terminal portion of internal carotid middle cerebral artery;
  • Informed consent from a parent or legal guardian and assent from the participant;
  • Acceptance to be followed for one year in the study. Hydroxyurea may be given for other reasons as part of the participant's ongoing care, but it will not be given as part of the study.

Exclusion Criteria for the treatment and control groups:

- Unable to commit to follow up visits for the course of the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01801423

Contacts
Contact: Michael R. DeBaun, MD, MPH 615-875-3040 m.debaun@vanderbilt.edu

Locations
Nigeria
Aminu Kano Teaching Hospital Recruiting
Kano, Nigeria, P.MB. 3452
Contact: Najibah Galadanchi, MBBS, FMCPath    234-803-700-5452    jibaliyu@yahoo.com   
Principal Investigator: Najibah Galadanchi, MBBS,FMCPath         
Sponsors and Collaborators
Vanderbilt University
Aminu Kano Teaching Hospital
Investigators
Principal Investigator: Michael R. DeBaun, MD, MPH Vanderbilt University
Principal Investigator: Muktar Aliyu, MBBS, MPH, DrPH Vanderbilt University
Principal Investigator: Lori Jordan, MD, PhD Vanderbilt University
  More Information

Publications:
Responsible Party: Michael DeBaun, Vice Chair for Clinical Research, JC Peterson Endowed Chair, Professor of Pediatrics and Medicine, Director, Vanderbilt-Meharry-Matthew Walker Center of Excellence in Sickle Cell Disease, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01801423     History of Changes
Other Study ID Numbers: 1R21NS080639-01, 1R21NS080639-01
Study First Received: February 26, 2013
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
transcranial Doppler
stroke
sickle cell anemia
Nigeria
hydroxyurea
low income country

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Anemia, Sickle Cell
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014